GTPase KRas (KRAS)
The protein contains 189 amino acids for an estimated molecular weight of 21656 Da.
Ras proteins bind GDP/GTP and possess intrinsic GTPase activity (PubMed:20949621). Plays an important role in the regulation of cell proliferation (PubMed:23698361, PubMed:22711838). Plays a role in promoting oncogenic events by inducing transcriptional silencing of tumor suppressor genes (TSGs) in colorectal cancer (CRC) cells in a ZNF304-dependent manner (PubMed:24623306). (updated: Aug. 12, 2020)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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Biological Process
Actin cytoskeleton organization
Activation of MAPKK activity
Axon guidance
Blood coagulation
Cytokine-mediated signaling pathway
Endocrine signaling
Epidermal growth factor receptor signaling pathway
Epithelial tube branching involved in lung morphogenesis
ERBB2 signaling pathway
Fc-epsilon receptor signaling pathway
Female pregnancy
Fibroblast growth factor receptor signaling pathway
Forebrain astrocyte development
Homeostasis of number of cells within a tissue
Innate immune response
Insulin receptor signaling pathway
Leukocyte migration
Liver development
MAPK cascade
Negative regulation of cell differentiation
Negative regulation of neuron apoptotic process
Neurotrophin TRK receptor signaling pathway
Positive regulation of cell population proliferation
Positive regulation of cellular senescence
Positive regulation of gene expression
Positive regulation of MAP kinase activity
Positive regulation of NF-kappaB transcription factor activity
Positive regulation of nitric-oxide synthase activity
Positive regulation of protein phosphorylation
Positive regulation of Rac protein signal transduction
Ras protein signal transduction
Regulation of long-term neuronal synaptic plasticity
Regulation of protein stability
Regulation of synaptic transmission, GABAergic
Response to glucocorticoid
Response to isolation stress
Response to mineralocorticoid
Small GTPase mediated signal transduction
Social behavior
Stimulatory C-type lectin receptor signaling pathway
Striated muscle cell differentiation
Vascular endothelial growth factor receptor signaling pathway
Visual learning
The reference OMIM entry for this protein is 190070
V-ki-ras2 kirsten rat sarcoma viral oncogene homolog; kras
Oncogene kras2; kras2
Kirsten murine sarcoma virus 2; rask2
C-kras v-ki-ras1 pseudogene, included; kras1p, included
Oncogene kras1, included; kras1, included
Kirsten ras1, included;
DESCRIPTION
The KRAS gene encodes the human cellular homolog of a transforming gene isolated from the Kirsten rat sarcoma virus. The RAS proteins are GDP/GTP-binding proteins that act as intracellular signal transducers. The most well-studied members of the RAS (derived from 'RAt Sarcoma' virus) gene family include KRAS, HRAS (190020), and NRAS (164790). These genes encode immunologically related proteins with a molecular mass of 21 kD and are homologs of rodent sarcoma virus genes that have transforming abilities. While these wildtype cellular proteins in humans play a vital role in normal tissue signaling, including proliferation, differentiation, and senescence, mutated genes are potent oncogenes that play a role in many human cancers (Weinberg, 1982; Kranenburg, 2005).CLONING
Der et al. (1982) identified a new human DNA sequence homologous to the transforming oncogene of the Kirsten (ras-K) murine sarcoma virus within mouse 3T3 fibroblast cells transformed by DNA from an undifferentiated human lung cancer cell line (LX-1). The findings showed that KRAS could act as an oncogene in human cancer. Chang et al. (1982) isolated clones corresponding to the human cellular KRAS gene from human placental and embryonic cDNA libraries. Two isoforms were identified, designated KRAS1 and KRAS2. KRAS1 contained 0.9 kb homologous to viral Kras and had 1 intervening sequence, and KRAS2 contained 0.3 kb homologous to viral Kras. McCoy et al. (1983) characterized the KRAS gene isolated from a human colon adenocarcinoma cell line (SW840) and determined that it corresponded to KRAS2 as identified by Chang et al. (1982). The KRAS2 oncogene was amplified in several tumor cell lines. McGrath et al. (1983) cloned the KRAS1 and KRAS2 genes and determined that the KRAS1 gene is a pseudogene. The KRAS2 gene encodes a 188-residue protein with a molecular mass of 21.66 kD. It showed only 6 amino acid differences from the viral gene. Comparison of the 2 KRAS genes showed that KRAS1 is lacking several intervening sequences, consistent with it being a pseudogene derived from a processed KRAS2 mRNA. The major KRAS2 mRNA transcript is 5.5 kb. Alternative splicing results in 2 variants, isoforms A and B, that differ in the C-terminal region. Alternative splicing of exon 5 results in the KRASA and KRASB isoforms. Exon 6 contains the C-terminal region in KRASB, whereas it encodes the 3-prime untranslated region in KRASA. The differing C-terminal regions of these isoforms are subjected to posttranslational modifications. The differential posttranslational processing has profound functional effects leading to alternative trafficking pathways and protein localization (Carta et al., 2006).GENE STRUCTURE
McGrath et al. (1983) first reported that the KRAS2 gene spans 38 kb and contains 4 exons. Detailed sequence analysis showed that exon 4 has 2 forms, which the authors designated 4A and 4B. The KRAS2 gene has been shown to have a total of 6 exons. Exons 2, 3, and 4 are invariant coding exons, whereas exon 5 undergoes alternative splicing. KRASB results from exon 5 skipping. In KRASA mRNA, exon 6 encodes the 3-prime untranslated region. In KRASB mRNA, exon 6 encodes the C-terminal region (Carta et al., 2006).MAPPING
By in situ hybridization, Popescu et al. (1985) mapped the KRAS2 gene to chromosome 12p12.1-p11.1. By linkage with RFLPs, O'Connell et al. (1985) confirmed the approximate location of KRAS2 on 12p12.1. - Pseudogene Th ... More on the omim web site
Aug. 24, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for KRAS
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 190070 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed